Conditions have been developed for: (a) in vitro stimulation of influenza virus-immune cytotoxic effector cells in human peripheral blood leukocyte (PBL) populations; and (b) measurement of effector cell activity on virus-infected cryopreserved human PBL target cells. Effector cells generated by in vitro stimulation with one type A influenza virus A/HKx31 (H3N2) were cytotoxic for autologous target cells infected with both A/HKx31 and a serologically distinct type A influenza virus PR8 A/Puerto Rico/8/34 (HON1), but did not kill cells infected with a type B influenza virus (B/Hong Kong). Conversely, effector cells generated against B/Hong Kong lysed B/Hong Kong, but not A/HKx31 or PR8 virus-infected autologous cells. These results indicate that the human T cell response to influenza viruses may be type-specific. They also appear to be restricted to recognize self components.